Bicyclo[2.2.1]heptane, 2-ethyl-5-methoxy-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 09 May 1988 and 23 May 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

403-610-9

EC Name:

-

Cas Number:

122795-41-9

IUPAC Name:

1-ethyl-3-methoxytricyclo[2.2.1.0²,⁶]heptane; 2-ethyl-5-methoxybicyclo[2.2.1]heptane; 2-ethyl-6-methoxybicyclo[2.2.1]heptane

Test material form:

liquid

Test animals

Species:

rat

Strain:

other: Crl:CD (SD) BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River U.K. Limited, Margate, Kent, England.
- Age at study initiation: Approximately seven to ten weeks of age
- Weight at study initiation: 217 to 250 g prior to dosing (Day 1)
- Fasting period before study:
- Housing:Housed individually in metal cages with wire mesh floors.
- Diet: S tandard laboratory rodent diet (Labsure LAD 1) ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: The mean daily minimum and maximum temperatures of the animal room were 21°C and 24°C
- Humidity: Mean daily relative humidity value was 58%.
- Air changes: Approximately 15 air changes/hour
- Photoperiod: 2 hours artificial light in each 24 hour period.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
One day prior to treatment hair was removed from the dorsolumbar region of each rat with electric clippers exposing an area equivalent to 10% of the total body surface. No shaving or chemical depilation was used.
The test substance was applied by spreading it evenly over the prepared skin. The treated area (aproximately 50 x 50 mm) was then promptly covered with gauze which was held in place with an impermeable dressinq encircled firmly around the trunk.

REMOVAL OF TEST SUBSTANCE
At the end of the 24-hour exposure period, the dressings were carefully removed and the treated area of skin decontaminated by washing in warm (30°-40°C) water and blotting dry with absorbent paper.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Ethyl methoxy norbornane was administered, as supplied by the Sponsor, at a volume of 2.11 ml/kg (S.G. 0.95).

Duration of exposure:

24 hours

Doses:

2.0 g/kg body weight

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external
examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths among a group of ten rats (five males and five females) given a single dermal dose of ethyl methoxy norbornane at 2.0 g/kg bodyweight.

Clinical signs:

other: There were no clinical signs of systemic reaction to treatment.

Gross pathology:

Terminal autopsy findings were normal.

Other findings:

Dermal responses
The sites of application of the test substance showed no irritation reactions or other dermal changes.

Applicant's summary and conclusion

Interpretation of results:

other: not acute harmful according to EU CLP (EC 1272/2008 and its amendments)

Conclusions:

The acute lethal dermal dose to rats of Neoproxen was found to be greater than 2.0 g/kg bodyweight.

Executive summary:

The acute dermal toxicity of Neoproxen was determined in a GLP study according to OECD Guideline 402. There were no deaths or signs or systemic toxicity or dermal irritation. No abnormalities were noted at necropsy. The acute lethal dermal dose to rats of Neoproxen was found to be greater than 2.0 g/kg bodyweight.